Bladder nuclear matrix proteins, polynucleotide sequences encoding them, and their use
Nuclear matrix proteins (NMP) which are characterized by a defined expression in tissue are provided. These NMPs are useful markers in diagnosing and monitoring the stage of malignancy of a cell and treating cell proliferative disorders associated with the NMP. Also provided are substantially purified polypeptides and nucleotide sequences encoding the NMPs of the invention.
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Claims
1. A purified nuclear matrix protein which is present in cancerous bladder cells but absent in normal bladder cells selected from the group consisting of:
- (a) BLCA-1 having a molecular weight of about 72 kD and a pI of about 7.70,
- (b) BLCA-2 having a molecular weight of about 40 kD and a pI of about 7.50,
- (c) BLCA-3 having a molecular weight of about 39 kD and a pI of about 6.27,
- (d) BLCA-4 having a molecular weight of about 37 kD and a pI of about 6.24,
- (e) BLCA-5 having a molecular weight of about 29 kD and a pI of about 5.80, and
- (f) BLCA-6 having a molecular weight of about 22 kD and a pI of about 8.00.
2. The protein of claim 1, wherein the protein is BLCA-1 having a molecular weight of 72 kD and a pI of 7.70.
3. The protein of claim 1, wherein the protein is BLCA-2 having a molecular weight of 40 kD and a pI of 7.50.
4. The protein of claim 1, wherein the protein is BLCA-3 having a molecular weight of 39 kD and a pI of 6.27.
5. The protein of claim 1, wherein the protein is BLCA-4 having a molecular weight of 37 kD and a pI of 6.24.
6. The protein of claim 1, wherein the protein is BLCA-5 having a molecular weight of 29 kD and a pI of 5.80.
7. The protein of claim 1, wherein the protein is BLCA-6 having a molecular weight of 22 kD and a pI of 8.00.
8. The protein of claim 2, comprising the amino acid sequence of SEQ ID NO:1.
9. The protein of claim 5, comprising the amino acid sequences of SEQ ID NO:2 and SEQ ID NO:3.
10. The protein of claim 7, comprising the amino acid sequence of SEQ ID NO:4.
11. The protein of claim 1, wherein the protein is isolated using two-dimensional gel electrophoresis.
12. An immunogenic fragment of a purified nuclear matrix protein which is present in cancerous bladder cells but absent in normal bladder cells, wherein said protein selected from the group consisting of:
- (a) BLCA-1 having a molecular weight of about 72 kD and a pI of about 7.70,
- (b) BLCA-2 having a molecular weight of about 40 kD and a pI of about 7.50,
- (c) BLCA-3 having a molecular weight of about 39 kD and a pI of about 6.27,
- (d) BLCA-4 having a molecular weight of about 37 kD and a pI of about 6.24,
- (e) BLCA-5 having a molecular weight of about 29 kD and a pI of about 5.80, and
- (f) BLCA-6 having a molecular weight of about 22 kD and a pI of about 8.00,
13. The fragment of claim 12, wherein the protein is BLCA-1 having a molecular weight of 72 kD and a pI of 7.70.
14. The fragment of claim 12, wherein the protein is BLCA-2 having a molecular weight of 40 kD and a pi of 7.50.
15. The fragment of claim 12, wherein the protein is BLCA-3 having a molecular weight of 39 kD and a pI of 6.27.
16. The fragment of claim 12, wherein the protein is BLCA-4 having a molecular weight of 37 kD and a pI of 6.24.
17. The fragment of claim 12, wherein the protein is BLCA-5 having a molecular weight of 29 kD and a pI of 5.80.
18. The fragment of claim 12, wherein the protein is BLCA-6 having a molecular weight of 22 kD and a pI of 8.00.
19. The fragment of claim 13, comprising the amino acid sequence of SEQ ID NO:1.
20. The fragment of claim 16, comprising the amino acid sequences of SEQ ID NO:2 and SEQ ID NO:3.
21. The fragment of claim 18, comprising the amino acid sequence of SEQ ID NO:4.
22. The fragment of claim 12, wherein the protein is isolated using two-dimensional gel electrophoresis.
23. A method of producing an antibody that differentiates between cancerous and normal bladder cells, comprising
- selecting a protein of claim 1 as an antigen,
- raising an antibody against said antigen, and
- recovering said antibody.
24. The method as claimed in claim 23, wherein the antibody is a monoclonal antibody.
25. A method of producing an antibody that differentiates between cancerous and normal bladder cells, comprising
- selecting a fragment of claim 12 as an antigen,
- raising an antibody against said antigen, and
- recovering said antibody.
26. The method as claimed in claim 25, wherein the antibody is a monoclonal antibody.
| 87/03910 | July 1987 | WOX |
| 93/09437 | May 1993 | WOX |
| 94/00573 | January 1994 | WOX |
| 94/18222 | August 1994 | WOX |
| 95/16919 | May 1995 | WOX |
- Getzenberg et al., "Identification Of Nuclear Matrix Proteins In The Cancer And Normal Rat Prostate", Cancer Research, vol. 51:6514-6520, (1991). CUPO, "Electrophoretic Analysis Of Nuclear Matrix Proteins And The Potential Clinical Applications", Journal of Chromatography, vol. 569:389-406, (1991). Gordon et al., "Organizations of Overlying Human Bladder urothelial Cells", Cancer Research, vol. 53(2):4971-4977, (1993). Konety et al. "Identification of Nuclear Matrix Protein Alterations Associated wit Renal Cell Carcinoma" The Journal of Urology, vol. 159, No. 4, pp. 1359-1363 (Apr. 1998). Eberharter et al. "Nuclear Matrix of the Lower Eurkaryote Physarum polycephalum and the Mammalian epithelial LLC-PK.sup.1 cell line," European Journal of Biochemistry, vol. 212, No. 2, pp. 573-580 (Mar. 1993). Getzenberg et "Bladder Cancer-associated Nuclear Matrix Proteins," Cancer Research, vol. 56, No. 7 pp. 1690-1694 (Apr. 1996). Keesee et al. "Utilization of Nuclear Matrix Proteins for Cancer Diagnosis," Critical Reviews in Eukaryotic Gene Expression, vol. 6, Nos. 2/3, pp. 189-214 (1996).
Type: Grant
Filed: Nov 1, 1996
Date of Patent: Feb 2, 1999
Assignee: University of Pittsburgh (Pittsburgh, PA)
Inventors: Robert H. Getzenberg (Pittsburgh, PA), Robert H. Bahnson (Pittsburgh, PA)
Primary Examiner: Karen Cochrane Carlson
Law Firm: Foley & Lardner
Application Number: 8/742,850
International Classification: C07K 1400;
